Diffuse Optical Imaging (DOI) allows us access to the hemodynamic response in tissue. It has been shown that we can by detecting the effects of neuro-vascular coupling relate this to functional events in the brain. Existing technologies in DOI are limited by a variety of factors, but most strongly by the absence of viable clinical applications where they may be applied. We have over the last year identified two key groups where functional optical imaging would be the only available functional tool, thus providing DOI with a real and necessary clinical use. These groups are young epilepsy sufferers who have had radical hemispherectomies and veterans with penetrating Traumatic Brain Injury (TBI). In identifying these groups we have also been examining the current shortcomings of DOI. These limitations are related to absolute quantitation of oxy/de-oxy hemoglobin in tissue and the problems surrounding physiological noise and the instrument-user interface. In the case of our two patients populations these factors will be key to developing viable tools. A further limitation of DOI is the depth of penetration, in this work we consider this an advantage in our move towards real-time imaging. We have identified an approach that uses the lack of depth to reduce the complexity of the inverse problem in a manner that unlike existing foreshortening techniques does not bias the data. The challenge in DOI in our patient groups is the presence of non diffusive sub-domains such as cerebro-spinal fluid and metallic fragments. These inclusions strongly affect the data and when modeled with existing diffusive models produce inaccurate data. We have developed theoretical models to handle this aspect of the modeling problem with some success. The next step will be to characterize their effect on the inverse problem. We must also consider quantitation as a key issue if we are to address neuro-plasticity or long term variational effects in functional imaging. No current imaging system can really provide accurate absolute data on the strength and locality of a functional event. We have begun work on a novel algorithm that shows the possibility to be able to absolutely reconstruct information and provide enhanced localization of the effect. Currently we are working on construction of a fiber based imaging system in collaboration with NINDS. The hardware is being developed based on new theoretical models of how to handle the fiber connection angle problem in DOI. A novel headset is being designed which should give greater control and accuracy over fiber placements involving a multi component headset with sectioned formed panels. Various mathematical models are currently under investigation to accelerate the imaging process towards real-time. An engineering based FEM using regular grids with irregular surfaces is being developed. This will reduce memory costs and simplify the meshing procedure making imaging faster and more efficient. This will also couple directly to the deformable plate model allowing the use of generic head models for specific patients. In collaboration with Drexel University, we are currently working on a novel LRD based system. Using the techniques developed for our fiber based model we aim to use novel LRDs with an enhanced dynamic range to create a wearable DOI interface. Such a system will involve wireless technologies to transmit data from a moving subject to an imaging base station and should radically change the available paradigms to functional imaging. Existing techniques exist in optical imaging to handle background physiological noise from tissues not of interest (e.g. scalp and skull). Various approaches including model-based systems and using short range source detectors averaged over the head are currently used. We are developing a model that will use information derived from unique access to 'noise only'data in hemispherectomy patients to infer how useful such models are. We aim to test inter and intra patient models and determine how statistically significant these effects are and whether generic models or background averaging are sufficient. Finally we have submitted an Invention Report relating to a novel instrument design intended to detect hematomas. It is designed to assist in the triage of patients with all forms of TBI. The ability to identify and triage for the presence of hematoma would greatly increase efficiency of use of more expensive and limited access systems such as CT and MRI. The development of this instrument into an imaging system capable of mapping the hematoma would also be beneficial in the case of the need for emergency in field surgery to remove pressure and in countries where economic limits mean access to CT and MRI is not standard and is under investigation.